Abstract
AbstractStudies have confirmed that circular RNA (circRNA) has a stable closed structure, which plays an important role in the progression of tumors. Cancers with positive fusion genes can produce associated fusion circRNA (F-cirRNA). However, there are no reports concerning a role for F-circRNA of the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1 (EML4-ALK1) in non-small cell lung cancer (NSCLC). Our study confirmed the existence of fusion circEA1 (F-circEA1) in NCI-H3122 cells (carrying the EML4-ALK1 gene), F-circEA1 was expressed both in the cytoplasm and nucleus as determined by fluorescence in situ hybridization (FISH) and Sanger sequencing. CCK8 and transwell assays showed that F-circEA1 was beneficial to cell proliferation, metastasis, and invasion. Overexpression of F-circEA1 can also promote cell proliferation, migration and invasion in A549 and SPCA1 cells (non-small cell lung cancer cell line not carrying the EML4-ALK1 gene). Interference with F-circEA1, induced cell cycle arrest and promoted apoptosis as determined by flow cytometry, and increased drug sensitivity to crizotinib in H3122 cells. F-circEA1 directly affected the expression of parental gene EML4-ALK1. Further research found that F-circEA1 can affect the downstream signaling pathway of ALK. In vivo, the growth rate of xenogeneic tumors was reduced and the protein expression level of EML4-ALK1 was significantly decreased in transplanted tumors measured by immunohistochemistry (IHC) after interference with F-circEA1. In conclusion, F-circEA1 can be considered as a proto-oncogene that regulates cell proliferation and apoptosis by affecting the expression of the parental gene EML4-ALK1 and its ALK downstream signaling pathway in non-small cell lung cancer.
Funder
National Natural Science Foundation of China
Senior Talent Foundation of Jiangsu University
Nanjing Medical Science and Technology Development Project
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology
Cited by
9 articles.
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